Screening for Barrett's Esophagus and Hereditary Cancer Syndromes

Key Takeaways:

• Screening for Barrett’s esophagus is challenging and should include upper endoscopy

• Reflux is a known cause of Barrett’s esophagus that can lead to esophageal cancer

• Risk factors for esophageal cancer among individuals with Barrett’s esophagus include male gender, age >50 years, history of chronic reflux, and a family history of esophageal cancer

• About 40% of patients with Barrett’s esophagus are asymptomatic

• Approximately 40% of individuals with esophageal cancer reported no symptoms of reflux

• Around 85% of patients with pancreatic cancer have random gene mutations, and approximately 15% have a familial component, with screening recommended in the following groups:

  • Those with a BRCA1 mutation and Lynch syndrome 

  • Those with a BRCA2 mutation and a first-degree relative 

  • Those with a PRSS1 mutation and Peutz-Jeghers syndrome

  • Those with two family members with the disease, with one of them being a first-degree relative 

• In patients at high risk for pancreatic cancer, annual screening with alternating endoscopic ultrasonography (EUS) one year and magnetic resonance imaging (MRI) the other year is recommended

• Patients with Lynch syndrome should be screened for hereditary gastrointestinal (GI) cancers

  • These individuals usually have a germline mutation—that is, the DNA mismatch repair gene

  • Those with either colon cancer or endometrial cancer who are younger than 50 years should be considered 

  • In these patients, screening for genetic mutations should be performed to check for stomach, small intestine, endometrial, and renal pelvic cancers

This transcript has been edited for clarity.

Screening for a Barrett's esophagus is a challenging issue, in the sense that we know reflux is a cause of Barrett's and [can] lead to cancer, but the vast majority of patients with reflux don't have Barrett's. We know there are risk factors for patients most likely to have Barrett's and those most likely to progress to esophageal cancer. 

Those are [being] men, white, over 50, history of chronic reflux—defined as symptoms at least weekly for over 5 years—as well as a family history of esophageal cancer. For those patients, the risk of having Barrett's is high enough [that] an upper endoscopy is widely regarded as necessary. The difficulty is that about 40% of patients with Barrett's have no symptoms at all. 

In keeping with those numbers, roughly 40% of patients with esophageal cancer had no reflux symptoms at all. So, the difficulty in our screening guidelines that suggest screening men over 50 with chronic reflux is [that] we're certainly going to miss almost half the patients with Barrett's that could progress to cancer. We don't have great guidelines on how to fill in that gap. I think the feeling is that if there are any symptoms of reflux at all in any patient over 45 or 50, we want to guarantee that patient does not have Barrett's, and upper endoscopy is likely necessary. 

The other thing is that while Barrett's and esophageal cancer are more likely in men, roughly 25% of the patients in our cohort here at Georgetown and [in] other studies around the country have Barrett's esophagus as well. 

Another cancer that's commonly brought up for screening is pancreatic cancer. With pancreatic cancer, patients are understandably concerned. Roughly 85% of the patients with [pancreatic] cancer have random gene mutations. Roughly 15% have a familial component. 

So, there are some patients with [a] relatively high risk, and they benefit from annual screening. Those are patients who have a BRCA2 mutation and a first-degree relative with pancreatic cancer, those patients with a BRCA1 mutation and Lynch syndrome, and also the less common patients with hereditary pancreatitis with a PRSS1 mutation and Peutz-Jeghers syndrome. 

Additionally, those are patients with two family members with pancreatic cancer, one of them being a first-degree relative. In that body of patients who are high-risk, the feeling is that some type of annual screening is reasonable. While there hasn't been any data to prove which regimen is best, the feeling is that alternating EUS one year with MRI the next year is a reasonable approach, recognizing that there's not data to suggest that this increases mortality. 

The other group of patients to screen for hereditary [GI] cancers are those with Lynch syndrome. Those are patients with a germline mutation—the DNA mismatch repair gene. The keys to a patient with Lynch syndrome would be some with either a colon cancer or an endometrial cancer younger than 50. In those patients, screening for genetic mutations is very important to identify other organs that would have a high risk of cancer, which would affect screening—primarily those of the stomach, small intestine, endometrial, and renal pelvic cancers as well.